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FLASH GENE
Symbol SPINK5 contributors: mct/npt - updated : 11-05-2018
HGNC name serine protease inhibitor, Kazal type 5
HGNC id 15464
Corresponding disease
NETS Netherton syndrome
Location 5q32      Physical location : 147.443.534 - 147.516.925
Synonym name
  • lympho-epithelial Kazal type related inhibitor
  • hemofiltrate peptide HF6478
  • hemofiltrate peptide HF7665
  • Synonym symbol(s) LETKI, VAKTI, ISK5, LEKTI, NETH, NETS, NS, FLJ21544
    DNA
    TYPE functioning gene
    SPECIAL FEATURE opposite orientation
    STRUCTURE 73.40 kb     33 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    KIAA1311 5q32 KIAA1311 protein POU4F3 5q31-q32 POU domain, class 4, transcription factor 3 TCERG1 5q31 transcription elongation regulator 1 (CA150) GPR151 5q32 G protein-coupled receptor 151 PPP2R2B 5q31-q33 protein phosphatase 2 (formerly 2A), regulatory subunit B (PR 52), beta isoform MGC22688 5q32 hypothetical protein MGC22688 DPYSL3 5q32 dihydropyrimidinase-like 3 KIAA0555 5q32 dihydropyrimidinase-like 3 SPINK1 5q31 serine protease inhibitor, Kazal type 1 LOC391838 5 similar to low affinity N-formyl peptide receptor SCGB3A2 5q32 secretoglobin, family 3A, member 2 LOC389336 5 similar to AVLV472 LOC391839 5 similar to elongation factor 1 gamma SPINK5 5q32 serine protease inhibitor, Kazal type, 5 LOC340060 5q33.1 similar to alpha-5 collagen ECG2 5q33.1 similar to alpha-5 collagen FLJ13962 5q33.1 hypothetical protein FLJ13962 SP329 5q33.1 hypothetical protein SP329 HTR4 5q31-q33 5-hydroxytryptamine (serotonin) receptor 4 ADRB2 5q31.3 adrenergic, beta-2-, receptor, surface KIAA1985 LOC255187 5q33.1 hypothetical LOC255187 KIAA0843 FLJ36748 5q33.1 hypothetical protein FLJ36748 GRPEL2 5q33.1 GrpE-like 2, mitochondrial (E. coli) MGC3265 5q33.1 hypothetical protein MGC3265 IL17B 5q32-34 interleukin 17B CSNK1A1 13q13 casein kinase 1, alpha 1 LOC389337 5 similar to hypothetical protein 4933429F08 PERC 5q33.1 similar to hypothetical protein 4933429F08
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    28 - 2915 - 916 - 1999 10419450
  • SPINK5s
  • a shorter LEKTI isoform composed of only the first 13 domains
  • 34 - 3745 - 1094 - 1999 10419450
    33 - 3655 121 1064 - 1999 10419450
  • SPINK5m
  • having a longer isoform carrying a 30-amino-acid residue insertion between the 13th and 14th inhibitory domains
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     pharynx   highly
    Lymphoid/Immunethymus   highly
    Reproductivefemale systemexternal genitaliaBartholin gland  
    Respiratoryrespiratory tracttrachea  highly
    Skin/Tegumentskin appendageshairbulb  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    Epithelialbarrier lininguroepithelium  
    Epithelialbarrier liningepidermisstratum granulosum  Homo sapiens
    Epithelialsecretoryglandularexocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • fifteen potential inhibitory domains (thirteen exhibit a Kazal type derived four cysteine residues)
  • fourteen spacing segments
  • a signal peptide
  • HOMOLOGY
    interspecies ortholog to murine Lekti
    intraspecies
    Homologene
    FAMILY
  • serine protease inhibitor family
  • CATEGORY immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • extracellular matrice remodeling
  • in the skin, SPINK5, KLK7, and KLK5 were all found in the lamellar granule (LG) system, but were separately localized
  • basic FUNCTION
  • involved in skin and hair morphogenesis and anti-inflammatory and/or antimicrobial protection of mucous epithelia
  • key regulator of the proteolytic events occurring during epidermal barrier formation and hair development
  • multidomain serine protease inhibitor which plays a central role in skin permeability barrier and allergy
  • plays a crucial role in deciding the timing of desquamation of the skin, and its gene expression is limited at the very surface of the stratum granulosum (SG)
  • GATA3 is important for inhibition of proliferation and induction of differentiation of keratinocytes, but its effect on SPINK5 expression was indirect and GATA3 alone was insufficient for final differentiation of keratinocytes where full SPINK5 expression was observed
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • caspase 14 is a novel target for the protease inhibitor SPINK5
  • PRSS3 contributes to the desquamation process by activating KLKs and degrading the intrinsic KLKs' inhibitor SPINK5
  • the actions of KLK7 are tightly controlled by PI3 and SPINK5, which also inhibits KLK5, localizing protease activity to the stratum corneum
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) NETS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in squamous cell carcinoma of the head and neck
    Susceptibility
  • to atopic dermatitis (AD) and asthma
  • to challenge-proven IgE-mediated food allergy in infants
  • Variant & Polymorphism SNP
  • SNP increasing the risk of atopic dermatitis
  • 420K SPINK5 variant as a predisposing factor to atopic dermatitis, in combination with other genetic and environmental factors
  • association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS